Bradykinesia in dystonic hand tremor: kinematic analysis and clinical rating.

Introduction: Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT). Methods: The protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings. Results: Thirty-six subjects participated in the study (12 DT, 12 HC and 12 early-stage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group. Discussion: Clinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities.

Machine learning models for diagnosis of essential tremor and dystonic tremor using grey matter morphological networks.

BACKGROUND: Essential tremor (ET) and dystonic tremor (DT) are the two most common tremor disorders, and misdiagnoses are very common due to similar tremor symptoms. In this study, we explore the structural network mechanisms of ET and DT using brain grey matter (GM) morphological networks and combine those with machine learning models. METHODS: 3D-T1 structural images of 75 ET patients, 71 DT patients, and 79 healthy controls (HCs) were acquired. We used voxel-based morphometry to obtain GM images and constructed GM morphological networks based on the Kullback-Leibler divergence-based similarity (KLS) method. We used the GM volumes, morphological relations, and global topological properties of GM-KLS morphological networks as input features. We employed three classifiers to perform the classification tasks. Moreover, we conducted correlation analysis between discriminative features and clinical characteristics. RESULTS: 16 morphological relations features and 1 global topological metric were identified as the discriminative features, and mainly involved the cerebello-thalamo-cortical circuits and the basal ganglia area. The Random Forest (RF) classifier achieved the best classification performance in the three-classification task, achieving a mean accuracy (mACC) of 78.7%, and was subsequently used for binary classification tasks. Specifically, the RF classifier demonstrated strong classification performance in distinguishing ET vs. HCs, ET vs. DT, and DT vs. HCs, with mACCs of 83.0 %, 95.2 %, and 89.3 %, respectively. Correlation analysis demonstrated that four discriminative features were significantly associated with the clinical characteristics. CONCLUSION: This study offers new insights into the structural network mechanisms of ET and DT. It demonstrates the effectiveness of combining GM-KLS morphological networks with machine learning models in distinguishing between ET, DT, and HCs.

Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

BACKGROUND: Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor. METHODS: All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters. RESULTS: Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups. CONCLUSIONS: GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET.

Exploring Heading Direction Perception in Cervical Dystonia, Tremor, and Their Coexistence.

OBJECTIVE: Dystonias, characterized by excessive muscle contractions resulting in involuntary postures and movements, impact 3 million people globally, making them the third most common movement disorder. Often accompanied by tremors, dystonias have epidemiological links and non-motor features shared with isolated tremor, such as essential tremor. Both dystonia and tremor present with balance dysfunction and abnormal involuntary movements, potentially linked to abnormal cerebellar function. This study explores the perception of one's own linear movement, heading, particularly discrimination of heading direction, in isolated cervical dystonia, isolated tremor, and their combination. We compare such perception behavior in visual and vestibular domains, predicting that visual heading perception would be superior to vestibular heading perception. METHODS: Following the focus on the perception of heading direction, we used psychophysics techniques, such as two-alternative-forced-choice task, to examine perception of direction of one's own movements as they see isolated visual star-cloud movement (visual heading perception) and en bloc body movement (vestibular heading perception). We fitted a sigmoidal psychometric function curve to determine the threshold for visual or vestibular heading perception in our participants. RESULTS: Nineteen participants underwent a two-alternative forced-choice task in the vestibular and visual domains. Results reveal elevated vestibular heading perception thresholds in cervical dystonia with or without tremor, and isolated tremor compared to healthy controls. Vestibular heading perception threshold was comparable in cervical dystonia with tremor and isolated tremor, but it was even worse in isolated cervical dystonia. Visual heading perception, however, remained less affected all three conditions-isolated cervical dystonia, isolated tremor, and their combination. CONCLUSION: These findings indicate shared deficits and distinctions in the perception of linear translational heading across movement disorders, such as isolated cervical dystonia, tremor, or their combination, offering insights into their pathophysiology, particularly the involvement of cerebellum regions responsible for vestibular processing.

A Case Series of Isolated Smiling Tremor: What Is the Phenomenology?

BACKGROUND: Five cases of tremor only upon smiling have been reported where no facial tremor is present at rest, when talking, or with full smile. CASES: This report highlights four cases of tremor upon partial smiling, discusses the phenomenology of smiling tremor, and reviews the current literature. Four subjects with lower facial tremor present only upon smiling underwent movement disorders evaluation with video. Tremor frequencies were determined by parsing the video clips into 1-second intervals and averaging the number of oscillations per interval and were determined to be high-frequency 8 to 10 Hz irregular facial tremors with harmonic variations upon moderate effort in all cases. Slight or full-effort smiling did not elicit facial muscle oscillations. Subjects had no other signs of tremor, dystonia, or parkinsonism on examination or in family history. CONCLUSIONS: Tremor upon smiling only, or isolated smiling tremor, is a unique task- and position-specific tremor of the facial musculature.

The Optimal Targeting for Focused Ultrasound Thalamotomy Differs between Dystonic and Essential Tremor: A 12-Month Prospective Pilot Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is increasingly used to treat drug-resistant essential tremor (ET). Data on MRgFUS thalamotomy in dystonic tremor (DT) are anecdotal. OBJECTIVES: To investigate efficacy, safety, and differences in target coordinates of MRgFUS thalamotomy in DT versus ET. METHODS: Ten patients with DT and 35 with ET who consecutively underwent MRgFUS thalamotomy were followed for 12 months. Although in both groups the initial surgical planning coordinates corresponded to the ventralis intermediate (Vim), the final target could be modified intraoperatively based on clinical response. RESULTS: Tremor significantly improved in both groups. The thalamic lesion was significantly more anterior in DT than ET. Considering both ET and DT groups, the more anterior the lesion, the lower the odds ratio for adverse events. CONCLUSIONS: MRgFUS thalamotomy is safe and effective in DT and ET. Compared to classical Vim coordinates used for ET, more anterior targeting should be considered for DT.

Dual target deep brain stimulation for complex essential and dystonic tremor - A 5-year follow up.

BACKGROUND: Essential tremor (ET) is characterized by action tremor of the upper limbs, head tremor and voice tremor. Dystonic tremor (DT) is produced by muscle contractions in a body affected by dystonia. Deep brain stimulation (DBS) of ventral intermediate nucleus of the thalamus (VIM) is the most well-known advanced treatment for medication-refractory tremor. However, decline in efficacy overtime has led to explore other targets. This study aimed to measure the efficacy of bilateral dual targeting ViM/caudal Zona Incerta (cZI) stimulation on tremor control. A secondary aim was to evaluate if there was a difference in the efficacy between ET and DT. METHODS: 36 patients were retrospectively recruited at the Walton NHS Foundation Trust, Liverpool, UK. Patients were assessed pre-operatively, and then at 1-year, 3-years, and 5-years post-operatively with the following scales: Fahn-Tolosa-Marin tremor rating (FTMTR) scale, EuroQol-5D, and Hospital Anxiety and Depression Scale. RESULTS: Bilateral ViM-cZI DBS significantly improved overall tremor score by 45.1% from baseline to 3-years post-operatively (p < 0.001). It continued to show improvement in overall FTMTR score by 30.7% at 5-years but this failed to meet significance. However, there was no significant improvement of mood or quality of life (QoL) scores. ET group on average showed a significant better clinical outcome compared to the DT group (p > 0.001). CONCLUSIONS: Our study found that bilateral ViM-cZI DBS treatment had a favourable effect on motor symptoms sustained over the 5-years in tremor patients, especially in ET group. There was limited effect on mood and QoL with similar trends in outcomes for both tremor types.

Consistency is key: influence of skull density ratio distribution on the formation of clinically effective lesions and long-term tremor suppression following treatment with MR-guided focused ultrasound.

OBJECTIVE: Skull density ratio (SDR) influences the permeability of the skull to the ultrasound waves used in magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor. SDR values vary across the skull and the mean value is known to be predictive of sonication thermal increase. The aim of this investigation was to explore the effects of the SDR distribution on clinical outcomes following treatment with MRgFUS. METHODS: Data from 61 patients with essential or dystonic tremor treated with MRgFUS targeting the ventral intermediate nucleus (Vim) were retrospectively analyzed. Tremor suppression was assessed using the Clinical Rating Scale for Tremor (CRST) and hand tremor score (HTS). Vim ablation volume was measured on the T1-weighted MR image acquired both at 1 day and 12 months after treatment. The numerical distribution of SDR values measured for each element in the ultrasound transducer was quantified by calculating the mean, standard deviation, skewness, entropy, and kurtosis of the SDR histogram. The effect of the SDR metrics on change in CRST and HTS was examined using a linear mixed-effects model. Additionally, the effect of the regional distribution of SDR values was explored in an element-wise analysis between patients with above- and below-average tremor suppression. RESULTS: A significant positive effect was found between SDR kurtosis and improvement in CRST (ß = 0.33, p = 0.004) and HTS (ß = 0.38, p < 0.001). The effect was found to be significant at 1 month posttreatment (CRST: ß = 0.415, p = 0.008; HTS: ß = 0.369, p = 0.016), and at the most recent clinical follow-up (CRST: ß = 0.395, p < 0.001; HTS: ß = 0.386, p < 0.001). One hundred seventy-one significant elements were identified in the element-wise analysis. The mean percentage difference from the mean SDR in these elements was associated with improvement in CRST (ß = 0.27, p < 0.008) and HTS (ß = 0.27, p < 0.015). Higher SDR kurtosis was associated with increased lesion volume at 12 months (p = 0.040) and less reduction in volume relative to the day-1 lesion volume (p = 0.007). CONCLUSIONS: Greater SDR kurtosis was associated with larger, more stable lesions at 12 months posttreatment and increased tremor suppression at long-term follow-up. SDR kurtosis may provide a more meaningful prognostic factor than the mean SDR.

Outcomes of Focused Ultrasound Thalamotomy in Tremor Syndromes.

BACKGROUND: The current literature comparing outcomes after a unilateral magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy between tremor syndromes is limited and remains a possible preoperative factor that could help predict the long-term outcomes. OBJECTIVE: The aim was to report on the outcomes between different tremor syndromes after a unilateral MRgFUS thalamotomy. METHODS: A total of 66 patients underwent a unilateral MRgFUS thalamotomy for tremor between November 2018 and May 2020 at St Vincent's Hospital Sydney. Each patient's tremor syndrome was classified prior to treatment. Clinical assessments, including the hand tremor score (HTS) and Quality of Life in Essential Tremor Questionnaire (QUEST), were performed at baseline and predefined intervals to 36 months. RESULTS: A total of 63 patients, comprising 30 essential tremor (ET), 24 dystonic tremor (DT), and 9 Parkinson's disease tremor (PDT) patients, returned for at least one follow-up. In the ET patients, at 24 months there was a 61% improvement in HTS and 50% improvement in QUEST compared to baseline. This is in comparison to PDT patients, where an initial benefit in HTS and QUEST was observed, which waned at each follow-up, remaining significant only up until 12 months. In the DT patients, similar results were observed to the ET patients: at 24 months there was a 61% improvement in HTS and 43% improvement in QUEST compared to baseline. CONCLUSION: These results support the use of unilateral MRgFUS thalamotomy for the treatment of DT, which appears to have a similar expected outcome to patients diagnosed with ET. Patients with PDT should be warned that there is a risk of treatment failure. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Radiofrequency ablation of the pallidothalamic tract and ventral intermediate nucleus for dystonic tremor through the parietal approach.

Background: The thalamic ventral intermediate nucleus (Vim) and globus pallidus internus are far apart and cannot be captured using a single electrode. Case Description: We describe our experience with a patient with dystonic tremors of the head and upper and lower extremities who showed symptomatic improvement after radiofrequency (RF) ablation using a parietal lobe approach with a single trajectory to capture the pallidothalamic tract and Vim. A 46-year-old man developed head tremors at 41 and a right-sided neck tilt three years later. Five years after the onset of the head tremors, tightness of the larynx during speech and tremors in both the upper and lower limbs also appeared. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was 24, and the Fahn-Tolosa-Marin Tremor Rating Scale (FTM) score was 48. We captured the pallidothalamic tract and Vim along a single trajectory by locating the entry point in the inferior parietal lobule. One week after treatment, the TWSTRS and FTM scale scores were 9 (62.5%) and 30 (37.5%), respectively. No adverse events were observed. Conclusion: This case suggests that in dystonic tremors involving abnormalities of the basal ganglia-thalamo-cortical and cerebello-thalamo-cortical circuits, a single electrode can be used to approach both circuits through the parietal lobe approach.

Laryngeal Dystonia, Dystonic Tremor and Vocal Tremor: Three Different Entities.

OBJECTIVE: The main objective of this study was to compare the demographic and clinical characteristics of patients with laryngeal dystonia (LD), dystonic tremor (DT), and vocal tremor (VT). STUDY DESIGN: This was a retrospective longitudinal study. METHODS: Data analysis from every patient diagnosed with LD, DT, or VT from January 1, 2010, to September 30, 2022, at a tertiary hospital center. Differential diagnosis between these entities was clinical (clinical history, voice assessment, and endoscopy) and confirmed by laryngeal electromyography. RESULTS: A total of 87 patients were included in this study: 50 patients with LD, 23 with DT, and 14 with VT. Age at diagnosis was significantly lower in patients with LD, with a mean age of 56.2 years when compared to DT (67.6 years; P = 0.002) and VT (70.5 years; P = 0.009). Furthermore, VT had a higher female prevalence (92.9%) when compared with LD (52%; P = 0.011). LD was mainly adductor, with only two patients diagnosed with abductor LD, and DT was adductor in every case. Tremor direction in patients with VT was horizontal in 50% and mixed (horizontal + vertical) in 50%, while in DT was mixed in 65.2% and horizontal in 34.8%. LD was more commonly an isolated laryngeal movement disorder (78%) when compared to DT (47.8%; P = 0.015) or VT (28.5%; P < 0.001), which were more often secondary to generalized neurological disorders. There were no differences between groups on Voice Handicap Index-10, self-reported grade of dysphonia on a visual analogic scale (0-10), maximum phonation time, and G, R, B, A, and I in the GRBAS-I scale at diagnosis (P > 0.05). S was significantly higher in LD when compared to VT (P < 0.001) and nonsignificantly higher than in DT (P = 0.075). CONCLUSIONS: LD, DT, and VT seem to be different entities with different demographics and clinical characteristics.

The Spectrum of Non-Parkinsonian Tremor: A Registry at a Tertiary Care Teaching Institute.

Background: Tremors other than those associated with Parkinson's disease (non-parkinsonian tremor) are commonly observed in clinical settings. However, their frequency and clinical characteristics have rarely been reported. Objectives: To classify non-parkinsonian tremors based on the consensus statement on the classification of tremors, from the task force of the International Parkinson and Movement Disorder Society published in 2018. Methods: A prospective registry at a tertiary care teaching institute. Results: A total of 475 patients with non-parkinsonian tremors were recruited for the study. 67.57% (n = 321) of our patients were male and a family history of tremor was present in 20.84% (n = 99) of patients. Dystonic tremor (DT) was the most common non-parkinsonian tremor (33.26%). 27.78% of patients fulfilled the new classification criteria for essential tremor, with 13.47% classified as pure ET (ET) and 14.31% exhibiting neurological soft signs, leading to the classification of ET plus (ETP). Patients with ETP had more family history (57.35%) [vs DT (26.48%, p = 0.00004) and ET (10.93%, p = 0.00003], longer duration of disease [mean ± standard deviation (SD) = 9.53 ± 8.64 years] [vs DT (5.60 ± 5.93, p = 0.0003) and ET (6.38 ± 5.97, p = 0.01) years], and more severe tremor as measured by the essential tremor rating assessment scale total score [mean ± SD = 27.42 ± 11.70] [vs DT (23.50 ± 8.62, p = 0.007) and ET (22.12 ± 8.19, p = 0.007)] compared with patients with DT and ET. Conclusions: DT was the most common cause of non-parkinsonian tremor in our registry followed by essential tremor syndrome. ETP was more common than ET.

The Challenge of Choosing the Right Stimulation Target for Dystonic Tremor-A Series of Instructive Cases.

Background: Thalamic deep brain stimulation (DBS) is established for medically refractory tremor syndromes and globus pallidus stimulation (GPi-DBS) for medically refractory dystonia syndromes. For combined tremor and dystonia syndromes, the best target is unclear. Objectives: We present four patients with two different profiles whose clinical course demonstrates that our current analysis of clinical symptomatology is not a sufficient predictor of surgical success. Methods: Outcome parameters were assessed with observer-blinded video ratings and included the Fahn-Tolosa-Marin-Tremor Rating Scale (FTM-TRS) and the Unified Dystonia Rating Scale (UDRS). Results: Two patients with "predominant lateralized action tremor" of the hands and mild cervical dystonia showed no relevant tremor improvement after GPi-DBS, but UDRS improved (mean, 45%). Rescue ventral intermediate nucleus of the thalamus (Vim)-DBS electrodes were implanted and both patients benefited significantly with a mean tremor reduction of 51%.Two other patients with "axial-predominant action tremor of the trunk and head" associated with cervical dystonia underwent bilateral Vim-DBS implantation with little effect on tremor (24% reduction in mean FTM-TRS total score) and no effect on dystonic symptoms. GPi rescue DBS was implanted and showed a significant effect on tremor (63% reduction in mean FTM-TRS) and dystonia (49% reduction in UDRS). Conclusions: The diagnosis of dystonic tremor alone is not a sufficient predictor to establish the differential indication of GPi- or Vim-DBS. Further criteria (eg, proximal-distal distribution of tremor/dystonia) are needed to avoid rescue surgery in the future. On the other hand, the course of our patients encourages rescue surgery in such severely disabled patients if the first target fails.

Neuropathic Tremor in Guillain-Barré Syndrome.

Background: Neuropathic Tremor (NT) is a postural/kinetic tremor of the upper extremity, often encountered in patients with chronic neuropathies such as paraprotein-associated and hereditary neuropathies. Objectives: To describe the clinical and electrophysiological features of NT in a previously underrecognized setting- during recovery from Guillain-Barré Syndrome (GBS). Methods: Patients with a documented diagnosis of GBS in the past, presenting with tremor were identified from review of clinical records. Participants underwent structured, videotaped neurological examination, and electrophysiological analysis using tri-axial accelerometry-surface electromyography. Tremor severity was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. Results: We describe the clinical and electrophysiological features of 5 patients with GBS associated NT. Our cohort had a fine, fast, and slightly jerky postural tremor of frequency ranging from 8 to 10 Hz. Dystonic posturing and overflow movements were noted in 4/5 patients. Tremor appeared 3 months-5 years after the onset of GBS, when patients had regained near normal muscle strength and deep tendon jerks were well elicitable. Electrophysiological analysis of tremor strongly suggested the presence of a central oscillator in all patients. Conclusion: NT is not limited to chronic inflammatory or hereditary neuropathies and may occur in the recovery phase of GBS. The tremor is characterized by a high frequency, jerky postural tremor with dystonic posturing. Electrophysiological evaluation suggests the presence of a central oscillator, hypothetically the cerebellum driven by impaired sensorimotor feedback.

Dystonia and tremor: Do they have a shared biology?

Dystonia and tremor are the two most commonly encountered hyperkinetic movement disorders encountered in clinical practice. While there has been substantial progress in the research on these two disorders, there also exists a lot of gray areas. Entities such as dystonic tremor and tremor associated with dystonia occupy a major portion of the "gray zone". In addition, there is a marked clinical heterogeneity and overlap of several clinical and epidemiological features among dystonia and tremor. These facts raise the possibility that dystonia and tremor could be having shared biology. In this chapter, we revisit critical aspects of this possibility that may have important clinical and research implications in the future. We comprehensively review the points in favor and against the theory that dystonia and tremor have shared biology from clinical, epidemiological, genetic and neuroimaging studies.

Grey matter correlates of dystonic soft signs in essential tremor.

BACKGROUND: Questionable signs of dystonia are a common finding in patients with essential tremor (ET). Brain structural alterations in ET patients plus dystonic soft signs (ET + ds) in comparison to ET patients without dystonic soft signs (ET-ds) or patients with tremor associated with manifest dystonia (TAWD) have not been examined yet. Therefore, our study aims to explore alterations of brain grey matter in patients with ET + ds. METHODS: A total of 68 elderly patients with ET-ds (n = 32), ET + ds (n = 20) or idiopathic cervical dystonia with dystonia associated action tremor of the upper limbs (TAWD, n = 16) and 42 age-matched healthy controls underwent a clinical and electrophysiological assessment and 3T MRI. For grey matter alterations T1 MRI images were analysed by voxel-based morphometry. Additionally, regression analyses with clinical parameters (tremor frequency, severity and disease duration) were performed. RESULTS: VBM showed a significant increase of grey matter in the right lentiform nucleus in ET + ds and TAWD compared to HC and ET-ds. Further, an increase of cortical grey matter in the middle frontal gyrus in ET + ds was shown. The hypertrophy of the lentiform nucleus in ET + ds was correlated with disease severity and duration. CONCLUSION: Patients with ET + ds showed grey matter brain structural alterations similar to TAWD. Our findings suggest an involvement of the basal ganglia-cortical loop in ET + ds which may indicate a pathophysiological similarity with TAWD rather than ET.